HODGKINS DISEASE

1
HODGKINS DISEASE

• DR. FAWWAZ YASSIN

2
HD

• First described by Hodgkin in 1832
• Incidence 1.5/100,000 children and adolescents
• Bimodal age distribution with one peak between
  2nd and 3rd decade and another peak between
  5th-6th decade of life
• Rare in children lt 5 years

3
HD

• 5 of childhood malignancy
• Male Female 21 in children, adults almost equal
  MF
• Mixed cellularity (MC) Hodgkins Disease is more
  common at younger ages
• Clustering in some families
• More common in Immune deficiency patients(
  Ataxia-Telangiectasia, HIV)

4
HD/ EPSTEIN-BARR VIRUS

• EBV has been implicated in the causation of HD by
  epidimiologic and serologic studies
• Large proportion of HD patients have high titer
  of EBV-Ab titer
• EBV genome in Reed-Sternberg cells by in situ
  hybridization
• EBV-positive genome are more frequently observed
  in children lt 10 years
• Incidence of EBV-associated HD varies by ethnic
  background (93 Asians, 86 Hispanic, 46 Whites,
  17 African-American)

5
HD/ IMMUNOPHENOTYPE
6
HD/ CLINICAL PRESENTATION

• SIGNS SYMPTOMS
  PERCENTAGE OF PATIENTS
• Lymphadenopathy
  90
• Mediastinal mass
  60
• B symptoms
  30
• Fever, weight loss, night sweats
• Hepatosplenomegaly
  25
• Most commonly involved lymph nodes are the
  cervical and supraclavicular in 75
• Bone marrow is involved in 5 of patients

7
HD/ DIAGNOSTIC EVALUATION

• Physical examination with measurement of lymph
  nodes
• CBCD, ESR, renal and hepatic function, AP, LDH,
  serum ferritin
• Lymph node biopsy
• CXR with measurement of mediastinal ratio
• CT scan of neck, chest, abdomen and pelvis
• Bone marrow biopsy?
• Gallium scan in doubtful abdominal involvement
  and mediastinal involvement
• echocardiogram

8
HD/ANN ARBOR STAGING CLASSIFICATION

• Stage
  Definition
• l Involvement of a single lymph node
  region (l) or of a single
  extralymphatic organ or site (lE)
• ll Involvement of two or more lymph
  node regions on the same
  side of the
  diaphragm (ll) or localized involvement of an
  extralymphatic organ or site and one or more
  lymph node regions on the same side of the
  diaphragm (llE)
• lll Involvement of lymph node regions on
  both sides of the diaphragm (lll) which may be
  accompanied by involvement of the spleen (lllS)
  or by localized involvement of an extralymphatic
  organ or site (lllE) or both (lllSE)
• lV Diffuse or disseminated involvement of
  one or more extralymphatic organs or tissues with
  or without associated lymph node involvement
• B symptoms fever gt 38ºC for three consecutive
  days, drenching night sweats or unexplained loss
  10 or more of weight the preceding 6 months

9
HD/ TREATMENT

• HD is a highly curable disease with cure rates of
  gt 90
• Appropriate treatment depends on risk features at
  time of diagnosis (risk adapted therapy)
• Therapy may be radiotherapy, chemotherapy or
  combined modality
• Standard radiation dose of (36-40 Gy) produces
  unacceptable cosmetic and skeletal abnormalities
  in prepubertal children and high risk of
  subsequent breast ca in adolescent females
• Combined modality therapy using low dose
  radiation (15-25 Gy) is the most commonly used
  therapy

10
HD/ TREATMENT

• Evaluation of chemotherapy alone treatment is
  difficult because most reports describe outcome
  after nonrandom assignment
• Unfavorable prognostic factors
• - stage lllB, lV
• - B symptoms
• - bulky disease
• - high ESR gt50

11
HD/ TREATMENT

• Long term effects of treatment should be taken
  into consideration
• - treatment related second neoplasms (e.g.,
  AML, NHL and Ca breast)
• - infertility
• - growth consideration
• - long-term organ dysfunction (e.g.,
  thyroid, heart, lung)

12
HD/ TREATMENT

• Adolescent patients who have achieved maximum
  growth can be treated as adult patients
• Chemotherapy alone protocols for localized
  disease has been used in developing countries
  with some success (Lobo-Sanahuja F Medical and
  Pediatric Oncology 22(6)1994)

13
TREATMENT RESULTS OF NORTH AMERICAN PEDIATRIC
COMBINED MODALITY TRIALS


Outcome/yr Chemotherapy
Radiation Rx Stage
patients EFS DFS RFS
SurvivStanford 3 MOPP/3ABVD
15-25 Gy,IF CS/PS l-lV
57 96 /6.7 - -
93/6.7 6 MOPP
15-25 Gy,IF PS l-lV
55 - -
90/15 89St. Jude 4-5 COPP/3-4 ABVD
20 Gy, IF CS ll-lV
85 - 93/5
- 93Pediatric Onco. Gp 4
MOPP/4 ABVD -
CS/PS llB,lllA,lllB-lV 80
80/5 - - 87 4
MOPP/4 ABVD 21 Gy, total
CS/PS llB,lllA,lllB-Vl 62 77/3
- - 91
lymphoid
irrad. Toronto 6 MOPP
20-30 Gy, EF CS l-lllA
57 - -
80/10 85
25-30 Gy, EF CS lllB-
lVCCG 6 ABVD
21Gy, EF PS lll-lV
54 87/4 -
- 90 12 ABVD
21Gy, regional PS lll-lV
64 87/3 -
- 89Intergroup Hodgkins 6 MOPP
35Gy, IF
PS l-ll 97
- - 95/5 90
14
HD

• Early stage HD stage l and llA
• It is not clear which combinations of treatment
  strategies are most effective at maintaining high
  cure rates and minimizing long term sequelae
• The Cochrane Library 2002 Intervention for
  early Hodgkins disease in children
• Four randomized controlled trials with 334
  patients
• There is little evidence from randomized clinical
  trials to evaluate the consensus approach of
  short course chemotherapy and local radiotherapy
• Significant failure rate when involved field
  irradiation is applied alone
• High ultimate survival in children with early
  stage HD

15
HD

• Combined modality treatment 2-4 courses of ABVD
  or Hybrid regimen IF radiation with 20-25 Gy.
  Oberlin O,J Clini Oncology(10)1992
• Combination chemotherapy with a proven regimen
  without radiation is currently under clinical
  evaluation (CCG-5942) 235 patients received IF
  radiation and 266 patients with no RT. The 3 yr
  EFS was 92.9 vs 86.1. The P value 0.006. No
  overall survival advantage. Study Progress Report
  2/2001
• Patients who have PR after initial therapy will
  receive 4 courses of COPP

16
HD

• Stage lllA
• Pediatric series support both the use of combined
  modality therapy and chemotherapy alone as
  initial management
• Radiation therapy may be indicated in patients
  with bulky disease at presentation or for
  residual disease after chemotherapy (Shellong G
  Annals of Oncology 71996)
• RT alone is inappropriate
• Combination chemotherapy alone. (Raney RB,J of
  Ped Hehatology/ Onconlogy 19(6)1997 )
• 6 courses of ABVD
• Patient who are slow responders (PR after 3 c)
  will be shifted to COPP or APPE

17
HD

• Stage lV and patients with B symptoms
• Combination chemotherapy is the treatment of
  choice
• Radiation therapy is sometimes added to areas of
  bulky disease
• Due to poor outcome of patients with stage lV
  they may benefit from enrollment in clinical
  trials
• ABVD or MOPP/ABVD total of 8 courses. Hutichinson
  RJ J Clini Onco 16(3),1998
• Slow responders will be individualized for APPE
  and radiation therapy ABMT

18
HD

• Recurrent/Refractory Childhood HD
• Treatment failure a. primary refractory dis.
• b. early relapse
  lt 1yr of .
  complete remission
• c. late relapse
• Patients with primary refractory disease and
  those relapsing after 6 cycles of chemotherapy
  would benefit of chemotherapy followed by
  peripheral stem cell transplant. Baker KS,et al
  J Clin Onco. 17(3)1999
• Chemotherapy regimens high dose Ara-ccisplatin
  or ifosfamide, carboplatin and etoposide .
  Gemcitabine has shown promising activity as a
  single agent